“I think it’s really interesting, but I’m worried about how long the treatment will last,” says Denica Milanova, founder of Marble Therapeutics, a Boston-based startup that also does gene therapy. She says collagen forms fibers in the skin that last about two or three months.

Milanova also believes that the ointment only works because it is applied to raw wounds, where the underlying layers, including skin stem cells, are exposed and can take on new genes. “But you can’t rub it on healthy skin, it won’t work,” she says. This is because normal skin acts as a barrier, a fact that may explain why in Krystal’s anti-wrinkle tests, her gene therapy is injected into the skin with a needle.

herpes virus

Scientists now have a plethora of tools to manipulate genes in their labs, where fixing cells in a dish or even treating mice for lethal conditions is commonplace. But the problem with treating people is that it’s harder for them to get the corrected DNA into their bodies, a problem known as gene delivery.

Krystal is among dozens of companies looking for innovative ways to deliver replacement genes to more places in the human body, including hard-to-reach organs like the brain.

“Delivery is the most important factor in genetic medicine,” says Max Chatsko, founder of Solt DB, a publishing and investment analytics company that also buys and sells biotech stocks (including Krystal). “I think this could eventually be the first dose of gene therapy that people take at home.”

Delivery of a gene typically involves placing a strand of DNA inside a virus naturally adapted to enter a human cell and release the gene. In Crystal’s case, the company uses the herpes simplex virus, the same virus that causes cold sores.

HSV-1, as the virus is known, is very common – about half of the people in the world are infected with it. This means that it is quite safe, but it also has the advantage that it naturally eludes the immune system. Krishnan says this property allows the drug to be used multiple times without causing negative reactions.

While the startup was successful, Chatsko says there was also some controversy over how he stumbled upon his strategy. In 2022, Krystal agreed to pay up to $75 million to another startup, PeriphaGen, which accused Krishnan and company steal his ideas and technologies.

Neeva, which for a while looked like one of the startups with a real chance to challenge the supremacy of Google Search, announced on Saturday that it was shutting down its search engine. The company says it is moving to artificial intelligence and could be acquired by Snowflake. information informed — but mostly seems to think it failed.

“Building search engines is hard,” Neeva co-founders Sridhar Ramaswami and Vivek Raghunathan wrote in blog post announcing the closure. (Ramaswami, in particular, is one reason Niva seemed promising—as a longtime head of Google’s advertising business, few people are better equipped to know how to build and monetize search than he is.) But Niva did it, they say. He built a good, competitive search engine. In fact, it was way ahead of Google in some respects, such as replacing 10 blue links with a more descriptive page and emphasizing human-generated content.

But building the search engine was actually the easy part. “During this journey, we discovered that building a search engine is one thing, and persuading ordinary users to choose the best option is one thing,” continued Ramaswami and Raghunathan.

I’ve spoken to Neeva’s co-founders several times over the past couple of years, and the list of complaints here is long and well-founded. They’ve had to contend with billions of dollars of deals that Google is signing up to make itself the default search engine on all devices; a huge “Are you sure you want to change?” pop-ups that appear whenever you try to set a new browser or default search engine; the difficulty of finding these settings in the first place; clutter in the Chrome Web Store; on and on and on. Anyone trying to create a new search engine is fighting a very uphill battle.

Neeva was also a paid product as the company tried to prove its business model for search other than ads and surveillance. “Contrary to popular belief,” the co-founders wrote on their blog, “convincing users to pay for a better experience was actually less of a challenge than getting them to try a new search engine.” Add to this the tough economic situation, and Niva simply does not see a way to develop the business.

The time here is really interesting. Neeva is shutting down, perhaps at the best time in two decades for upstart search engines. Users getting more and more bored with the ad load and poor quality results they get from Google, and AI-enabled chatbots like Bing and ChatGPT have upended the whole idea of ​​how to interact with the internet. Neeva has also capitalized on this by developing a large language model-based system called Neeva AI, which is more useful in many ways than what you get from Bing or Bard. But even this was not enough.

Of course, the race to beat Google is still on: Bing continues to work hard to gain market share, and Brave recently advertised that it now runs entirely on its own search stack. Companies such as you.com and DuckDuckGo are also trying to rethink the way search works and use artificial intelligence to do this. But for now, it looks like Google’s only real competitor is, well, Google.

The Neeva search engine will be closed on June 2nd. In the future, Neeva will “switch into a new area of ​​activity” that is likely to be based on an LLM and linked to the acquisition of Snowflake. The Company will refund users for the unused portion of their Neeva subscriptions and delete all user data. “We are truly grateful to our community,” the co-founders wrote, “and we are truly sorry that we cannot continue to provide the search engine you want and deserve.”